Abstract: The present invention relates to a binding compound which binds to human APRIL. More specifically the invention provides, compositions of anti-APRIL specific antibodies and methods to use such antibodies in modulating the biological activity APRIL, particularly in inflammatory diseases, inhibition of cell proliferation and cancer.

Abstract: Methods of treating cancers comprising FGFR1 gene amplification are provided. In some embodiments, the methods comprise administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and/or an FGFR1 ECD fusion molecule. In some embodiments, the methods comprise administering a fibroblast growth factor receptor 1 (FGFR1) extracellular domain (ECD) and/or an FGFR1 ECD fusion molecule in combination with at least one additional therapeutic agent.

Abstract: The present invention provides methods for improving the treatment effect of a chemotherapy regimen of a patient suffering from HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer, by adding bevacizumab (Avastin®) to a chemotherapy regimen by determining the expression level, in particular the blood plasma expression level, of VEGFA and/or VEGFR2 relative to control levels of patients diagnosed with HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer. The present invention also provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level, in particular the blood plasma expression level, of VEGFA and/or VEGFR2 relative to control levels in patients diagnosed with HER2 positive breast cancer, in particular locally recurrent or metastatic HER2 positive breast cancer.

Abstract: The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.

Abstract: Provided herein are pro-VP antagonists, such as antibodies and antigen-binding portions thereof specific for pro-VP, for identifying and targeting expressing cancer cells. Applicants additionally provide methods of using said compositions, for example to image cancer cells in vivo and in biological samples. The compositions may also be used for treating patients suffering from a provasopressin-expressing cancer. Provasopressin-expressing cancers include neuroendocrine cancer, pancreatic cancer, and prostate cancer.

Abstract: The present invention is directed to methods of treating or preventing a metabolic disease or disorder and cardiovascular complications and other complications thereof by administering agents that inhibit the NOTCH signaling pathway. In addition, the invention encompasses methods for determining whether a patient is at increased risk for developing these conditions by determining the amount, function, or activity of NOTCH pathway components in biological samples derived from the patient or in imaging analysis.

Abstract: The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-? receptor agonist or an IFN-? receptor agonist, for the treatment of cancer.

Abstract: The present invention relates to improved Nanobodies™ against Tumor Necrosis Factor-alpha (TNF-alpha), as well as to polypeptides comprising or essentially consisting of one or more of such Nanobodies. The invention also relates to nucleic acids encoding such Nanobodies and polypeptides; to methods for preparing such Nanobodies and polypeptides; to host cells expressing or capable of expressing such Nanobodies or polypeptides; to compositions comprising such Nanobodies, polypeptides, nucleic acids or host cells; and to uses of such Nanobodies, such polypeptides, such nucleic acids, such host cells or such compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes.

Abstract: Methods are disclosed for increasing the binding affinity of binding proteins using in silico affinity maturation.

Abstract: The present invention relates to the treatment of ocular diseases and conditions by administering a complement pathway inhibitor, particularly an alternative pathway inhibitor. Ocular diseases include age-related macular degeneration, diabetic retinopathy, and ocular angiogenesis. One embodiment comprises the administration of an anti-Factor D antibody in the form of a whole antibody, a Fab fragment or a single domain antibody. Other complement component inhibitors that may be useful in the present method include Factor H or inhibitors that block the action of properdin, factor B, factor Ba, factor Bb, C2, C2a, C3a, C5, C5a, C5, C6, C7, C8, C9, or C5b-9.

Abstract: Proteins that bind to matrix metalloproteinase 14, combination therapies with such proteins and methods of using such proteins are described.

Abstract: This disclosure relates, at least in part, to a method of treatment. In one embodiment, the method of treatment comprises administering to a subject in need of such treatment a first therapeutic agent including compound (1): or a pharmaceutically acceptable salt thereof in combination with a second therapeutic agent, wherein the first therapeutic agent and the second therapeutic agent are administered either simultaneously or sequentially.

Abstract: The present invention is drawn to antibody-mediated modulation of allergy. In this regard, the present invention discloses a monoclonal antibody, antigen-binding fragment or mimic thereof directed against Group 1 pollen allergens or homologues thereof. Also disclosed herein is the mechanism by which the disclosed monoclonal antibody, antigen binding fragment or mimic thereof will improve immunotherapy of allergic reactions in an individual. It is contemplated that herein that such a monoclonal antibody, antigen binding fragment or mimic thereof may also be useful in treatment of several microbial infections.

Abstract: Methods for treating cancer comprising administering a DLL4 antagonist and one or more anti-hypertensive agents are described. Also described are pharmaceutical compositions comprising a DLL4 antagonist and one or more anti-hypertensive agents, and kits comprising the same.

Abstract: The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 are negative regulators of ?-catenin and the Wnt signaling pathway in eukaryotic cells. The activity of ZNRF3 can be modulated by antibody binding to its extracellular domain, thus causing an increase in Wnt signaling. The ZNRF3 antagonizing antibodies can be used to treat diseases with low Wnt signaling, such as short bowel syndrome, osteoporosis, diabetes, neurodegenerative diseases, and mucositis. In addition, the antagonizing antibodies of the invention can be used to enhance Wnt signaling for tissue repair and wound healing.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: Disclosed are methods and compositions for preventing, treating, or ameliorating eosinophilic esophagitis (EoE) in an individual, comprising administering to the individual a therapeutically effective amount of at least one CRTH2 antagonist or a pharmaceutically acceptable salt thereof and at least one proton pump inhibitor (PPI) or a pharmaceutically acceptable salt thereof. Also disclosed are compositions comprising at least one CRTH2 antagonist or a pharmaceutically acceptable salt thereof and at least one proton pump inhibitor or a pharmaceutically acceptable salt thereof.

Abstract: Disclosed is an AGR2 blocking monoclonal antibody, and in particular, a humanized monoclonal antibody for blocking AGR2. Also disclosed is a pharmaceutical composition containing the antibody and a method for preparing the same, and a use of the antibody in blocking tumor growth and metastasis.

Abstract: The invention provides methods, uses and compositions for the treatment of ankylosing spondylitis (AS). The invention describes methods and uses for treating ankylosing spondylitis, wherein a TNF? inhibitor, such as a human TNF? antibody, or antigen-binding portion thereof, is used to reduce signs and symptoms of ankylosing spondylitis in a subject. Also described are methods for determining the efficacy of a TNF? inhibitor for treatment of ankylosing spondylitis in a subject.

Abstract: This disclosure demonstrates that blockade of TGF? signaling after a hematopoietic stress (e.g., chemotherapy, transplantation, and infection) accelerates hematopoietic reconstitution and delays the return of cycling hematopoietic stem and progenitor cells (HSPCs) to quiescence. TGF? blockade in these settings promotes multilineage hematopoietic regeneration by prolonging HSPC cycling and by promoting HSC self-renewal, and is useful for treating hematologic deficiencies caused various hematopoietic stresses.

Abstract: The invention relates to anti-VEGF polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating cancer and inflammatory disease, such as arthritis.

Abstract: The present invention relates to injecting a high specificity cytokine antagonist into a diseased intervertebral disc.

Abstract: The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.

Abstract: The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

Abstract: Methods for treating neurodegeneration, e.g., sensorineural hearing loss, or a demyelinating disease, using bisphosphonates, ERK kinase inhibitors, and osteoprotegerin (OPG) proteins or nucleic acids.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: The present invention relates to the induction of tolerance to antigens, by mucosal, preferably oral delivery of the antigen in combination with an immunomodulating compound producing micro-organism. More specifically, the invention relates to the induction of Foxp3+ and/or IL-10 and/or TGF-? producing regulatory T-cells, capable of suppressing undesired immune responses toward an antigen, by oral delivery of said antigen in combination with an immunosuppressing cytokine secreting micro-organism.

Abstract: Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

Abstract: Methods of treating disorders in which TNF? activity is detrimental via biweekly, subcutaneous administration of human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor ? (hTNF?) are disclosed. The antibody may be administered with or without methotrexate. These antibodies have high affinity for hTNF? (e.g., Kd=10?8 M or less), a slow off rate for hTNF? dissociation (e.g., Koff=10?3 sec?1 or less) and neutralize hTNF? activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Kits containing a pharmaceutical composition and instructions for dosing, and preloaded syringes containing pharmaceutical compositions are also encompassed by the invention.

Abstract: The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to EGFR on tumor cells that overexpress EGFR, and on tumor cells that express the truncated version of the EGFR receptor, de2-7 EGF. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.

Abstract: The present disclosure provides human monoclonal antibodies that bind specifically to CXCR4 with high affinity. This disclosure also provides a method for treating a subject afflicted with a CXCR4-expressing cancer, in particular a hematological malignancy such as multiple myeloma, acute myeloid leukemia, or non-Hodgkin's lymphoma, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an anti-CXCR4 antibody of the disclosure. The disclosure further provides a kit for treating a cancer in a subject comprising a dose of an anti-CXCR4 antibody and instructions for using the anti-CXCR4 antibody in the therapeutic methods of the disclosure.

Abstract: ROR2 is provided as a therapeutic target and prognostic marker for cancers, which include without limitation specific carcinomas and sarcomas. This invention also provides for the use of conjugates comprising an antibody that recognizes and binds ROR2, and a cytotoxic agent. In the cytotoxic conjugates, the cell binding agent has a high affinity for ROR2 and the cytotoxic agent has a high degree of cytotoxicity for cells expressing ROR2, such that the cytotoxic conjugates of the present invention form effective killing agents. In a preferred embodiment, the cell binding agent is an anti-ROR2 antibody or an epitope-binding fragment thereof, more preferably a humanized anti-ROR2 antibody or an epitope-binding fragment thereof, wherein a cytotoxic agent is covalently attached, directly or via a cleavable or non-cleavable linker, to the antibody or epitope-binding fragment thereof.

Abstract: The present invention provides compositions and methods which involve specifically antagonizing GDF8 and Activin A. In certain embodiments, compositions are provided which comprise a GDF8-specific binding protein and an Activin A-specific binding protein. For example, the invention includes compositions comprising an anti-GDF8 antibody and an anti-Activin A antibody. In other embodiments, antigen-binding molecules are provided which comprise a GDF8-specific binding domain and an Activin A-specific binding domain. For example, the invention includes bispecific antibodies that bind GDF8 and Activin A. The compositions of the present invention are useful for the treatment of diseases and conditions characterized by reduced muscle mass or strength, as well as other conditions which are treatable by antagonizing GDF8 and/or Activin A activity.

Abstract: A method for treating a patient suffering from inflammation, chronic inflammation, pain, rheumatoid arthritis (RA), osteoarthritis and osteoporosis, comprising administering an effective amount of a selective inhibitor of the 11-?-hydroxysteroid dehydrogenase Type 1 enzyme.

Abstract: A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

Abstract: The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

Abstract: The present application provides a method for treating a neurodegenerative disease in a subject characterised in that the endoplasmic reticulum protein retrotranslocation machinery and/or VCP is modulated by administering to said subject a therapeutically effective amount of a modulator of said endoplasmic reticulum protein retrotranslocation machinery and/or of VCP.

Abstract: The invention features methods for preventing or treating visceral pain, including pain associated with functional bowel disorder, inflammatory bowel disease and interstitial cystitis, by administering an anti-CGRP antagonist antibody.

Abstract: Antibodies against influenza neuraminidase, compositions containing the antibodies, and methods of using the antibodies are provided herein.

Abstract: Methods of treating a patient suffering from psoriasis are disclosed, comprising administration of an antibody binding to interleukin-12 (IL-12).

Abstract: The present invention relates generally to antibodies cross-reactive with IL-17A and IL-17F, and bispecific anti-IL-17A/F and their uses.

Abstract: The invention relates to methods and compositions for the modulation of glucose homeostasis and/or the treatment of metabolic diseases. In some embodiments, the invention relates to methods and compositions for the modulation of histone deacetylases. such as Class IIa histone deacetylases.

Abstract: Methods are provided for treating dementia and or impaired cognition, as well as assays useful for identifying novel anti-dementia agents. Compounds and compositions for treating dementia and or impaired cognition are also provided.

Abstract: The present disclosure relates generally to compositions and methods for treating cancer with a glucopyranosyl lipid A (GLA) in the absence of antigen.

Abstract: The present invention provides methods of treating cancer, particularly cancers that are null or have decreased expression or activity of the Lkb1 gene. Also included are methods of identifying therapeutic targets for the treatment of cancer.

Abstract: The invention includes novel methods of treating or preventing fibrosis in a subject afflicted with scleroderma, comprising administering to the subject a therapeutically effective amount of an agent that inhibits formation of at least one inflammasome signaling product in the subject.

Abstract: Method of detecting individuals at risk for atherosclerosis and related vascular diseases involving the detection of IL-1? autoantibodies, as well as therapeutic methods to prevent or treat atherosclerosis and related vascular disease by administering a pharmaceutical composition comprising IL-1? autantibodies.

Abstract: The invention concerns antibodies directed against CD127, I.e. the alpha chain of the receptor for interleukin7 (IL-7), especially the receptor for human IL-7 expressed on human cells (designated human IL-7R alpha or IL-7Ra) or the TSLP receptor. The antibodies of the invention have cytotoxic activity against CD127 positive cells. The invention also relates to the use of these antibodies in order to deplete subpopulations of T lymphocytes as a result of cytotoxic action of the antibodies, through ADCC and optionally through CDC. Accordingly the invention concerns the use of the antibodies in the treatment of transplant rejection, autoimmune diseases, allergic diseases, lymphoma or cancer when these pathologies are associated with CD127 positive cells.

Abstract: The present invention relates to methods for diagnosing and treating Myhre Syndrome. The invention provides a method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises detecting a mutation in SMAD4 gene, as compared to a control population, wherein the presence of said mutation is indicative of Myhre Syndrome or of a risk of Myhre Syndrome. The present invention also relates to an inhibitor of the SMAD4-mediated TGF?/BMP signalling pathway for use in the treatment of Myhre Syndrome.

Abstract: The present invention relates to chimeric (preferably, bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds preferably covalently bind to the urokinase receptor and recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and/or antibody-dependent cellular cytotoxicity (ADCC) against a large number and variety of cancers, thus providing cancer cell death and/or an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.